Analysis of the brain transcriptome, microbiome and metabolome in ketogenic diet and experimental stroke

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity Pub Date : 2024-10-06 DOI:10.1016/j.bbi.2024.10.004

Anastasia A. Zharikova , Nadezda V. Andrianova , Denis N. Silachev , Vladimir O. Nebogatikov , Irina B. Pevzner , Ciara I. Makievskaya , Ljubava D. Zorova , Grigoriy V. Maleev , Galina V. Baydakova , Dmitry V. Chistyakov , Sergey V. Goriainov , Marina G. Sergeeva , Inna Y. Burakova , Artem P. Gureev , Vasily A. Popkov , Aleksey A. Ustyugov , Egor Y. Plotnikov

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引用次数: 0

Abstract

The ketogenic diet (KD) has been shown to be effective in treating various brain pathologies. In this study, we conducted detailed transcriptomic and metabolomic profiling of rat brains after KD and ischemic stroke in order to investigate the effects of KD and its underlying mechanisms. We evaluated the effect of a two-month KD on gene expression in intact brain tissue and after middle cerebral artery occlusion (MCAO). We analyzed the effects of KD on gut microbiome composition and blood metabolic profile as well as investigated the correlation between severity of neurological deficits and KD-induced changes. We found transcriptional reprogramming in the brain after stroke and KD treatment. The KD altered the expression of genes involved in the regulation of glucose and fatty acid metabolism, mitochondrial function, the immune response, Wnt-associated signaling, stem cell development, and neurotransmission, both in intact rats and after MCAO. The KD led to a significant change in the composition of gut microbiome and the levels of amino acids, acylcarnitines, polyunsaturated fatty acids, and oxylipins in the blood. However, the KD slightly worsened the neurological functions after MCAO, so that the therapeutic effect of the diet remained unproven.

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生酮饮食与实验性中风的脑转录组、微生物组和代谢组分析。

生酮饮食（KD）已被证明能有效治疗各种脑部病变。在本研究中，我们对 KD 和缺血性中风后的大鼠大脑进行了详细的转录组和代谢组分析，以研究 KD 的影响及其潜在机制。我们评估了为期两个月的 KD 对完整脑组织和大脑中动脉闭塞（MCAO）后基因表达的影响。我们分析了 KD 对肠道微生物组组成和血液代谢谱的影响，并研究了神经功能缺损的严重程度与 KD 引起的变化之间的相关性。我们发现中风和 KD 治疗后大脑中的转录重编程。KD 改变了参与调节葡萄糖和脂肪酸代谢、线粒体功能、免疫反应、Wnt 相关信号传导、干细胞发育和神经传导的基因的表达，无论是在完整大鼠中还是在 MCAO 后都是如此。KD导致肠道微生物组的组成以及血液中氨基酸、酰基肉碱、多不饱和脂肪酸和氧脂素的水平发生了显著变化。然而，KD 会轻微恶化 MCAO 后的神经功能，因此该饮食的治疗效果仍未得到证实。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain, Behavior, and Immunity 医学-免疫学

CiteScore

29.60

自引率

2.00%

发文量

290

审稿时长

28 days

期刊介绍： Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.